Дисертації з теми "Gene dependency"
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1
Ikeda, Hiroki. "Clock gene defect disrupts light-dependency of autonomic nerve activity." Kyoto University, 2008. http://hdl.handle.net/2433/124223.
2
Lazaridis, Konstantinos. "Investigation of the Smad-dependency for protease and inhibitor gene expression in response to TGF-β1." Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410505.
3
Huang, Alice. "Calcium-sensing Receptor Mediated Control of CYP27B1 Promoter-dependent Gene & Protein Expression: Complex Extracellular Ca2+ Concentration Dependence." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/20127.
Анотація:
Changes in extracellular Ca2+ (Ca2+o) differentially modulate 25-hydroxyvitamin D3 1α-hydroxylase (1αOHase; encoded by CYP27B1) mRNA and protein levels in cell types including the renal proximal tubule (inhibitory), parathyroid, and skeletal osteoblasts (stimulatory) to control 1,25-dihydroxyvitamin D3 synthesis. We hypothesised that the calcium-sensing receptor (CaSR) mediated Ca2+o concentration-dependent control of 1αOHase, either directly through Ca2+o, or through the local production of parathyroid hormone related peptide (PTHrP). To investigate promoter activity, I transfected a firefly luciferase reporter gene under the control of the 1501 bp human CYP27B1 promoter into HEK-293 cells that stably expressed the CaSR (HEK-CaSR cells) and measured luciferase activities from cells exposed to various Ca2+o concentrations. CYP27B1 promoter-controlled luciferase expression exhibited a biphasic Ca2+o-dependent response in luciferase activity and protein that peaked with a 2-fold increase from basal levels at around 3.0 mM Ca2+o in HEK-CaSR cells. This response was absent in HEK-293 cells and was shifted to the left or right in the presence of the CaSR positive allosteric modulator, cinacalcet, or negative allosteric modulator, NPS-2143, respectively, indicating that both the stimulatory and inhibitory phases were CaSR-mediated. Firefly luciferase and 1αOHase mRNA levels obtained from quantitative RT-PCR exhibited a monophasic Ca2+o-dependent increase and suggests that the stimulatory phase arises from increased mRNA expression, whereas the inhibitory phase arises from reduced protein levels. Inhibitor and mutational studies suggested that the stimulatory phase was dependent on Gq/11 signalling, whereas the inhibitory phase requires MEK and PKC-dependent phosphorylation of the crucial T888 site of the CaSR's C-terminal tail.
4
Tronnersjö, Susanna. "Functional studies of RNA polymerase II-dependent transcription in yeast Saccharomyces cerevisiae /." Uppsala : Department of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/2006109.pdf.
5
Yeğin, Zeynep Arslanoğlu Alper. "Hiv-1 regulatory gene dependent expression of a toxic gene/." [s.l.]: [s.n.], 2006. http://library.iyte.edu.tr/tezlerengelli/master/biyoloji/T000556.pdf.
6
Lori, Toju William Peter. "Ca²⁺-dependent gene expression and epilepsy." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613662.
7
Johansson, Anna. "Dependence-induced changes in opioid-receptor gene expression." Thesis, Linköpings universitet, Institutionen för fysik, kemi och biologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-90034.
Анотація:
Using drugs such as alcohol and morphine among others can be addictive in some individuals, and progress into a substance abuse disorder. The mesolimbic dopaminergic system (MD-system) is involved in the reward process during the development of drug addiction. The MD-system is critical for survival and affects different behaviors in both man and animal. Neurochemical pathways drive for instance physical activity, food intake, love and reproduction and are part of the natural reward process involved partly in the release of dopamine (DA) into frontal lobes. Within the MD-system opioid receptors throughout the brain are affected by drug intake, and activation of these receptors modulate DA-release in brain regions involved in reward-behavior. The aim of this study was to evaluate gene expression of MOR and DOR within the endogenous opioid system (EO-system) in relation to voluntary physical activity, a natural reinforcer. Further on investigations of the drug alcohol was compared to the natural reinforcer sucrose using voluntary consumption. For both experiments qRT-PCR was used to measure mRNA levels of MOR and DOR from brain areas of interest. We found a small significant up regulation in NAc, PFC and VTA but for DOR in VTA a down regulation in gene expression of physical exercising mice. Additionally these two different genes OPRM1- and the OPRD1- gene are down regulated in VTA and NAc due to alcohol- and sugar-intake. This implicate that the natural reward system and their ORs point in the direction of earlier findings; the opioid receptors have a key role in regulate alcohol intake and the natural rewarding stimuli as food intake.
8
He, Jie. "Isolation of An ARGONAUTE Gene in Pelargonium and Identification Of Candidate Genes Regulated Through ARGONAUTE4-Dependent RNA-Dependent DNA Methylation In Arabidopsis." Connect to full text in OhioLINK ETD Center, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=toledo1260812913.
Анотація:
Dissertation (Ph.D.)--University of Toledo, 2009.Typescript. "Submitted as partial fulfillment of the requirements for the Doctor of Philosophy degree in Biology." Bibliography: leaves 54-56, 91-95, 118-119, 133-139.
9
Lin, Jialiang. "Cordycepin affects growth factor-dependent gene expression." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/50823/.
Анотація:
The natural compound cordycepin (3’-deoxyadenosine) causes a reduction in breast cancer cell viability. Microarray analysis showed that growth related genes are down-regulated by cordycepin. Indeed, mTOR, ERK and AMPK signalling was shown to be altered by cordycepin, but the effect was too fast to be mediated by transcriptional changes. It was hypothesised that cordycepin affected signal transduction through translation. However, polysome profiling did not identify clear candidates for the effects of cordycepin on signal transduction but unveiled that cordycepin leads to translation repression on 5’ terminal oligopyrimidine (TOP) mRNAs. As TOP mRNAs are known to be regulated by mTOR signaling, this result consistently suggests mTOR signaling is inhibited by cordycepin treatment. To test if it is possible that cordycepin affects gene expression via signal transduction, we compared its effects to various signal transduction inhibitors and an activator. So far, Pictilisib, a pan-PI3K inhibitor, is the only inhibitor that mimics both the gene expression and signal transduction effects of cordycepin, indicating the PI3K-PDK1-AKT axis is affected by cordycepin. The RNAs upregulated by cordycepin were highly enriched in a group of non-coding RNAs, which are also appeared to induce during serum withdrawal. Knockdown of poly(A) polymerases induced these RNAs, indicating that they probably are degraded by the PABPN1 and poly(A) polymerase dependent nuclear RNA decay pathway. Thus the data suggest that cordycepin affects gene regulation by two distinct pathways, one affecting signal transduction and growth related mRNA expression and another affecting polyadenylation mediated decay of non-coding mRNAs.
10
Farris, Sean. "Myelin Gene Expression: Implications for Alcohol Abuse and Dependence." VCU Scholars Compass, 2012. http://scholarscompass.vcu.edu/etd/322.
Анотація:
Acute behavioral responses to ethanol have predictive value for determining an individual's risk of long-term drinking behavior. Although the neurobiology of alcohol abuse is complex, prior studies from our laboratory demonstrated differential myelin-associated gene expression (MAGE) in medial prefrontal cortex (PFC) as one potential mechanism influencing acute ethanol behaviors between C57BL/6J (B6) and DBA/2J (D2) mice. Our laboratory and others have also shown MAGE is reduced in PFC of alcoholics. Herein, I have extended these findings through expression profiling of PFC into chronic models of ethanol self-administration from non-human primates and mice. Together, these results suggest that regulation of MAGE may be relevant to behavioral phenotypes witnessed in alcoholism. The pathogenesis of alcoholism progresses through multiple stages of drug exposure and withdrawal, however, genetic predisposition is also a major contributing factor for this disease. Therefore, I tested the hypothesis that not only does ethanol have direct effects on MAGE, but also variation in basal MAGE within the PFC is a molecular endophenotype underlying ethanol behavioral sensitivity. Bioinformatics of basal MAGE across the BXD recombinant inbred panel (n=29), derived from B6 and D2 mice, revealed a densely correlated myelin gene network associated with several ethanol behavioral phenotypes. Literature association tools identified Fyn kinase as potential regulator of MAGE. Fyn knockout mice are known to be more sensitive to the sedative-hypnotic properties of ethanol in the loss of righting reflex (LORR) paradigm. Microarray analysis of Fyn knockout mice revealed a significant decrease in MAGE, suggesting MAGE may be an underlying factor for LORR. In support of this premise, microarray analysis of genetic variance in LORR across Inbred Long Sleep and Inbred Short Sleep mice, as well as congenics for the Lore5 quantitative trait locus, also demonstrated an inverse relationship between MAGE and duration of LORR. The hypothesis was further investigated using cuprizone to model demyelination in B6 mice and test them in a battery of acute ethanol behaviors. Cuprizone-treated mice had a significantly greater duration in LORR (p < 0.01), demonstrating that myelin is an important contributor to the genetic variance in LORR. Thus, through genetic, genomic, and pharmacological tools I have ‘molecularly triangulated’ a myelin gene network as a contributing factor influencing acute ethanol behavioral sensitivity. The ability of myelin to alter acute ethanol sensitivity may warrant a prospective study of myelin in humans as a predictive molecular phenotype for an individual’s risk of developing alcohol dependence. Additionally, further genomic dissection of MAGE architecture and associated networks may aid in developing novel pharmacotherapies for an alcohol use disorder. Supported by NIAAA grants F31 AA018615 to SPF
11
Ma, Shengyun [Verfasser]. "Sirt6-dependent gene regulation of oncofetal gene loci in hepatocytes / Shengyun Ma." Mainz : Universitätsbibliothek Mainz, 2017. http://d-nb.info/1123047286/34.
12
Brunello, Marco. "Domain and genre dependency in Statistical Machine Translation." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8420/.
Анотація:
Statistical Machine Translation (SMT) is currently the most promising and widely studied paradigm in the broader field of Machine Translation, continuously explored in order to improve its performance and to find solutions to its current shortcomings, in particular the sparsity of big bilingual corpora in a variety of domains or genres to be used as training data. However, while one the main trends is still to rely as much as possible on already available large collections of data, even when they do not fit quite well specific translation tasks in terms of relatedness of content, the possibility of using less but appropriately selected training sets - depending on the textual variety of the documents that need to be translated case by case - has not been extensively explored as much so far. The goal of this research is to investigate whether this latter possibility, i.e. the lack of availability of large quantities of assorted data, can have a possible solution in the application of strategies commonly used in genre and domain classification (including unsupervised topic modeling and document dissimilarity techniques), in particular performing subsampling experiments on bilingual corpora in order to obtain a good fit between training data and the texts that need to be translated with SMT. For the purposes of this study, already existing freely available large corpora were found to be unsuitable for the selection of domain/document specifc subsamples, so two new parallel corpora - English-Italian and English-German - were compiled employing the \web as corpus" approach on websites containing translated content. Then some tests were made on documents belonging to different varieties, translated with SMT systems built using subsamples of training data selected using document dissimilarity measures in order to pick up the most suitable documents as training data. Such method has shown how the choice of subsampling strategy heavily depends on the text variety of each considered document, but it has also proven that better translation results can be obtained from small samples of training sets rather than using all the available data, which brings benefits also in terms of quicker training times and use of fewer computational resources.
13
Ashall, Louise. "Signal-dependent NF-kappaB dynamics modulate gene transcription." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494089.
14
Ashall, Louise. "Signal-dependenr NF-kappaB dynamics modulate gene transcription." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494088.
15
Bashkeel, Nasser. "Human Gene Expression Variability and Its Dependence on Methylation and Aging." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/38988.
Анотація:
The phenotypic variability in human populations is partly the result of gene polymorphisms and differential gene expression. Studying the variability of gene expression across human populations is essential to understanding the molecular basis for diversity. However, key issues remain unanswered with respect to human expression variability. For example, the role of gene methylation in expression variability is uncertain, nor is it clear what role tissue-specific factors may have. Moreover, the contribution that expression variability has in aging and development is unknown. Here we classified human genes based on their expression variability in normal human breast and brain samples and identified functional aspects associated with high and low expression variability. Interestingly, both high variability and low variability gene sets are enriched for developmentally essential genes. There is limited overlap between the variably expressed genes of different tissues, indicating that tissue-specific rather than individual-specific factors are at work. We also find that methylation likely has a key role in controlling expression variability insofar as genes with low expression variability are likely to be non-methylated. Importantly, we find that genes with high population expression variability are likely to have age-, but not sex-dependent expression. Taken together, our work indicates that gene expression variability is tissue-specific, methylation-dependent, and is an important component of the natural aging process.
16
Walker, Caray A. "Iron-dependent regulation of gene expression in Corynebacterium pseudotuberculosis." Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/1392/.
Анотація:
This study set out to analyse C. pseudotuberculosis within an environment relevant to that which would be encountered within its natural host. The impact of the availability of iron within the growth environment of numerous bacteria has been widely reported, and an equivalent investigation was conducted to determine whether the same was true of C. pseudotuberculosis. To this end, a novel chemically-defined medium was designed, which supported the growth of C. pseudotuberculosis, but in which the concentration of specific growth factors could be manipulated. Subsequently, iron was shown to be essential for C. pseudotuberculosis growth, and analysis of secreted protein profiles revealed differential expression between low- and high-iron growth conditions. Furthermore, growth experiments conducted in the defined medium revealed that C. pseudotuberculosis is capable of obtaining iron from the host iron-binding proteins, transferrin and lactoferrin. The results presented in this thesis confirm the importance of iron to C. pseudotuberculosis, and reveal the existence of an iron-dependent regulator which is involved in regulating the expression of multiple target genes.
17
Malkawi, Amir H. "Wall stress dependent gene espression in abdominal aortic aneurysms." Thesis, St George's, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558352.
Анотація:
Patient specific wall stress analysis demonstrated that wall stress was higher in AAA's at risk of rupture. Furthermore, there is a correlation between sites of rupture and high wall stress regions. We set out to investigate the gene expression in regions of high and low wall stress to identify the role of wall stress in the pathogenesis of AAA Methods Finite element analysis (PEA, ADINA R&D Inc., Watertown, USA) was performed on patients with AAA scheduled for open repair. Regions of high and low wall stress were identified from the obtained patient specific wall stress map. Coordinates of regions of high and low stress were mapped on a three-dimensional reconstruction of each aneurysm which included major visceral branches as reference points to aid in intra-operative localization. High and low stress regions were marked intra-operatively on the aneurysm surface according to their distance from the reference points and full-thickness biopsies were obtained. RNA was extracted (RNeasy Fibrous Tissue RNA Extraction Kit, Qiagen, UK) and whole genome profiling was performed (Illurnina HumanRef-8 v3.0 Expression BeadChips). Protein expression was determined by Western blotting. Results PEA was performed on 11 patients. Paired samples were obtained from high and low wall stress regions. AAA wall was found to be thinner in regions exposed to high wall stress. There was over-expression of LMNA (Larnin AlC) in high wall stress regions. Over-expression of lamin AlC was also demonstrated on Western blotting. Conclusion Our results identify novel pre-rupture changes in AAA's in regions exposed to high stress. This is the first study to identify a role for lamin AlC in AAA pathogenesis. Over expression of lamin A/C in high wall stress regions highlights the role of cytoskeletal and nuclear mechanics, mechanotransduction and apoptotic transcriptional pathways in AAA development and rupture.
18
Cheema, Manraj Singh. "Xenobiotic-dependent regulation of human karyopherin A2 (KPNA2) gene." Thesis, University of Surrey, 2011. http://epubs.surrey.ac.uk/843116/.
Анотація:
A common reaction to xenobiotic exposure is the modulation of genes that mediate the response to such insult, including the drug metabolising enzymes and drug transporters. This transcriptional response is typically mediated by the nuclear receptor family of ligand activated transcription factors, and the translocation of these key regulators into the nucleus, whether before or after ligand binding, is a pre-requisite for their activity. The karyopherin a family of adapter proteins (6 in man) form a molecular bridge between nuclear cargoes and the nuclear import machinery. Previous work demonstrated that the rat karyopherin a genes are themselves responsive to a number of xenobiotics, including classical nuclear receptor ligands. The aim of this study was to delineate the molecular mechanism underlying transcriptional regulation of human karyopherin a2 (KPNA2) gene. In silico analysis of the 2.6kb immediately upstream and including the first exon of human KPNA2 promoter revealed several putative transcription factor binding sites, most notably for the nuclear receptors vitamin D receptor (VDR), progesterone receptor (PR), retinoid related orphan receptor a (RORa), peroxisome proliferated activated receptor a (PPARa), glucocorticoid receptor a (GRa), pregnane X receptor (PXR) and hepatic nuclear factor 4 (HNF4) and the anti-oxidant response protein, Nrf2. Using a reporter gene assay in the human hepatoma cell line Huh7, preliminary experiments demonstrated that the KPNA2 gene was responsive to cognate ligands for many of these nuclear receptors, as well as oxidative stress-mediated activation of Nrf2. In-depth analysis including promoter deletion, site directed mutagenesis and electrophoretic mobility shift assay were carried out to determine the molecular mechanism underlying these transcriptional effect. The down-regulation of human KPNA2 expression by cyproterone acetate was mediated via GRa and not PXR whereas the down-regulation of human KPNA2 expression by Wy-14,643 was elicited not by its cognate nuclear receptor, PPARa but most likely via Nrf2 through the oxidative stress signaling pathway. In conclusion, these findings provide a rational explanation for the mechanistic basis of human KPNA2 gene regulation by a number of endobiotics and xenobiotics, and postulate the importance of this phenomenon for optimizing cellular response to these stimuli.
19
Myers, Stephen Anthony. "Kallikrein gene regulation in hormone-dependent cancer cell lines." Thesis, Queensland University of Technology, 2003. https://eprints.qut.edu.au/15842/1/Stephen_Myers_Thesis.pdf.
Анотація:
Hormone-dependent cancers (HDCs), such as those of the prostate, ovary, breast and endometrium, share characteristics that indicate similar underlying mechanisms of carcinogenesis. Through steroid hormone signalling on "down-stream" target genes, the growth, development and progression of HDCs are regulated. One such family of target genes, highly expressed in HDCs and regulated by steroid hormones, are the tissue kallikreins (KLKs). The KLKs are a multigene family of serine proteases involved in physiological processes such as blood pressure regulation, inflammation, and tumour development and progression via the hydrolysis of specific substrates. Although the KLK gene family is clearly implicated in tumourigenesis, the precise roles played by these genes are largely unknown. Additionally, except for the androgen-responsive genes, KLK2 and KLK3, the mechanisms underlying their hormonal regulation in HDCs are yet to be identified. The initial focus of this thesis was to examine the regulation of the kallikreins, KLK1 and KLK4, by estradiol and progesterone in endometrial and breast cancer cell lines. From these studies, progesterone clearly regulated KLK4 expression in T47D cells and therefore, the focus of the remaining studies was to further examine this regulation at the transcriptional level. An overview of the results obtained is detailed below. Human K1 and hK4 protein levels were increased by 10 nmol/L estradiol benzoate, progesterone, or a combination of the two, over 48 hours in the endometrial cancer cell line, KLE. However, these same treatments resulted in no change in KLK1 gene or hK1 protein levels in the endometrial cancer cell lines, HEC1A or HEC1B (only hK1 analysed). Progesterone treatment (0-100 nmol/L) over 24 hours resulted in a clear increase in KLK4 mRNA at the 10 nmol/L dose in the breast cancer cell line, T47D. Additionally, treatment of T47D cells with 10 nmol/L progesterone over 0-48 hr, resulted in the rapid expression of the hK4 protein at 2 hr which was sustained for 24 hr. Further analysis of this latter progesterone regulation with the antiprogesterone, RU486, over 24 hours, resulted in an observable decrease in hK4 levels at 1 µmol/L RU486. Although the estrogen and progesterone regulation of the hK1 protein was not further analysed, the data obtained for hK4 regulation in T47D cell lines, supported the premise that this gene was progesterone-responsive. The rapid expression of hK4 protein by progesterone at two hours suggests that KLK4 transcription is directly coupled to progesterone regulation, perhaps through progesterone receptor (PR) binding to progesterone-responsive regions within the KLK4 promoter or far "up-stream" regions. Thus, the following further studies were performed. To test this hypothesis, the transcription initiation site (TIS) and 5' flanking regions of the KLK4 gene in T47D cells were interrogated. Primer extension and 5' RACE identified the TIS 78 bp 5' of the putative ATG site for translation as identified by Korkmaz et al. (2001). This KLK4 gene transcript consists of only four exons, and thus excludes the pre/pro signal peptide. Although a TATA-box is not present within -25 to -30 bp 5' of the identified TIS, a number of consensus binding motifs for Sp1 and estrogen receptor half-sites were identified. It is possible that the Sp1 sites are involved in the basal levels of transcription for this gene. Additionally, a putative progesterone response element (PRE) was identified in the far "up-stream" regions of the KLK4 gene. Basal levels of transcription were observed within the KLK4 proximal promoter region when coupled to a luciferase reporter gene and transfected into T47D cell lines. Additionally, the KLK4 proximal promoter region did not induce the luciferase reporter gene expression when progesterone was added to the system, however, estradiol was inhibitory for luciferase gene expression. This suggests that the proximal promoter region of the KLK4 gene could contain functional EREs but not PREs. In keeping with this hypothesis, some ER half-sites were identified, but PR sites were not obvious within this region. The identified PRE in the far "up-stream" region of the KLK4 gene assembled the progesterone receptor in vitro, and in vivo, as assessed by electromobility shift assays and chromatin immunoprecipitation assays (EMSAs and ChIPs), respectively. The binding of the PR to the KLK4 PRE was successfully competed out by a PR antibody and not by an androgen receptor antibody, and thus confirms the specificity of the KLK4 PRE-PR complex. Additionally, the PR was recruited and assembled onto and off the progesterone-responsive KLK4 region in a cyclic fashion. Thus, these data strongly suggest that the PR represents one of the core components of a transcription complex for the KLK4 gene, and presumably also contributes to the expression of this gene. Moreover, these data suggest a functional coordination between the PR and the KLK4 progesterone-responsive region in T47D cells, and thus, provide a model system to further study these events in vivo.
20
Myers, Stephen Anthony. "Kallikrein Gene Regulation in Hormone-Dependent Cancer Cell Lines." Queensland University of Technology, 2003. http://eprints.qut.edu.au/15842/.
Анотація:
Hormone-dependent cancers (HDCs), such as those of the prostate, ovary, breast and endometrium, share characteristics that indicate similar underlying mechanisms of carcinogenesis. Through steroid hormone signalling on "down-stream" target genes, the growth, development and progression of HDCs are regulated. One such family of target genes, highly expressed in HDCs and regulated by steroid hormones, are the tissue kallikreins (KLKs). The KLKs are a multigene family of serine proteases involved in physiological processes such as blood pressure regulation, inflammation, and tumour development and progression via the hydrolysis of specific substrates. Although the KLK gene family is clearly implicated in tumourigenesis, the precise roles played by these genes are largely unknown. Additionally, except for the androgen-responsive genes, KLK2 and KLK3, the mechanisms underlying their hormonal regulation in HDCs are yet to be identified. The initial focus of this thesis was to examine the regulation of the kallikreins, KLK1 and KLK4, by estradiol and progesterone in endometrial and breast cancer cell lines. From these studies, progesterone clearly regulated KLK4 expression in T47D cells and therefore, the focus of the remaining studies was to further examine this regulation at the transcriptional level. An overview of the results obtained is detailed below. Human K1 and hK4 protein levels were increased by 10 nmol/L estradiol benzoate, progesterone, or a combination of the two, over 48 hours in the endometrial cancer cell line, KLE. However, these same treatments resulted in no change in KLK1 gene or hK1 protein levels in the endometrial cancer cell lines, HEC1A or HEC1B (only hK1 analysed). Progesterone treatment (0-100 nmol/L) over 24 hours resulted in a clear increase in KLK4 mRNA at the 10 nmol/L dose in the breast cancer cell line, T47D. Additionally, treatment of T47D cells with 10 nmol/L progesterone over 0-48 hr, resulted in the rapid expression of the hK4 protein at 2 hr which was sustained for 24 hr. Further analysis of this latter progesterone regulation with the antiprogesterone, RU486, over 24 hours, resulted in an observable decrease in hK4 levels at 1 µmol/L RU486. Although the estrogen and progesterone regulation of the hK1 protein was not further analysed, the data obtained for hK4 regulation in T47D cell lines, supported the premise that this gene was progesterone-responsive. The rapid expression of hK4 protein by progesterone at two hours suggests that KLK4 transcription is directly coupled to progesterone regulation, perhaps through progesterone receptor (PR) binding to progesterone-responsive regions within the KLK4 promoter or far "up-stream" regions. Thus, the following further studies were performed. To test this hypothesis, the transcription initiation site (TIS) and 5' flanking regions of the KLK4 gene in T47D cells were interrogated. Primer extension and 5' RACE identified the TIS 78 bp 5' of the putative ATG site for translation as identified by Korkmaz et al. (2001). This KLK4 gene transcript consists of only four exons, and thus excludes the pre/pro signal peptide. Although a TATA-box is not present within -25 to -30 bp 5' of the identified TIS, a number of consensus binding motifs for Sp1 and estrogen receptor half-sites were identified. It is possible that the Sp1 sites are involved in the basal levels of transcription for this gene. Additionally, a putative progesterone response element (PRE) was identified in the far "up-stream" regions of the KLK4 gene. Basal levels of transcription were observed within the KLK4 proximal promoter region when coupled to a luciferase reporter gene and transfected into T47D cell lines. Additionally, the KLK4 proximal promoter region did not induce the luciferase reporter gene expression when progesterone was added to the system, however, estradiol was inhibitory for luciferase gene expression. This suggests that the proximal promoter region of the KLK4 gene could contain functional EREs but not PREs. In keeping with this hypothesis, some ER half-sites were identified, but PR sites were not obvious within this region. The identified PRE in the far "up-stream" region of the KLK4 gene assembled the progesterone receptor in vitro, and in vivo, as assessed by electromobility shift assays and chromatin immunoprecipitation assays (EMSAs and ChIPs), respectively. The binding of the PR to the KLK4 PRE was successfully competed out by a PR antibody and not by an androgen receptor antibody, and thus confirms the specificity of the KLK4 PRE-PR complex. Additionally, the PR was recruited and assembled onto and off the progesterone-responsive KLK4 region in a cyclic fashion. Thus, these data strongly suggest that the PR represents one of the core components of a transcription complex for the KLK4 gene, and presumably also contributes to the expression of this gene. Moreover, these data suggest a functional coordination between the PR and the KLK4 progesterone-responsive region in T47D cells, and thus, provide a model system to further study these events in vivo.
21
Zarnegar, Parisa. "In vitro and postmortem studies of the brain opioid system: association to opiate dependence /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-904-1/.
22
Bohm, Rudy Ashish. "Transcriptional control of slowpoke, a calcium activated potassium channel gene /." Full text (PDF) from UMI/Dissertation Abstracts International, 2000. http://wwwlib.umi.com/cr/utexas/fullcit?p3004218.
23
Wong, Kwun-kit, and 黃冠傑. "The role of TSPYL2 on regulation of behavior and CREB-dependent gene expression." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hdl.handle.net/10722/208426.
Анотація:
TSPYL2 (Testis-specific Y-encoded-like protein 2) is a member of the
Nucleosome Assembly Protein (NAP) superfamily. It is a nuclear protein
expressed in the cerebral cortex and the hippocampus. Our group has generated
Tspyl2 knockout (Tspyl2m) mice, which are deficit in hippocampal long-term
potentiation (LTP) with downregulation of Nr2a and Nr2b. Since Nr2a and Nr2b,
subunits of the N-Methyl-D-Aspartate receptors, and hippocampal LTP are
important in learning and memory, our Tspyl2m mice are likely to have behavioral
deficits particularly in those related to memory. TSPYL2 could also affect LTP
via CREB-dependent gene expression, since other NAP members have shown
interaction with CBP/p300 - transcriptional co-activators of CREB which are
well-known to be involved in memory formation. Furthermore, TSPYL2 may be
linked to X-linked mental retardation (XLMR), since it is located at Xp11.2, a
region with a high density of XLMR genes; and one of its interacting partners,
CASK, is a XLMR gene.
This thesis examines the three issues mentioned above. First, to characterize
the behavior of our Tspyl2m mice, a behavioral test battery including open-field
with amphetamine challenge, social interaction, prepulse inhibition and fear
conditioning were conducted. Second, to examine the role of TSPYL2 on
CREB-dependent gene expression, I first examined the subcellular localization of
HA-TSPYL2 and endogenous CBP, p300 and pCREB in HEK293 cells. Then the
interactions between TSPYL2 and CBP were tested by mammalian two-hybrid
assay and co-immunoprecipitation. Thereafter, luciferase assay was used to
measure CRE-luc activity in HEK293 and NG108-15 cells with overexpression
and knockdown of TSPYL2. Third, to investigate the potential role of TSPYL2 on
XLMR, a mutation analysis on the TSPYL2 gene was conducted with a cohort of
82 male patients with unexplained mental retardation. The analysis included
examining the methylation on the TSPYL2 upstream sequence, DNA sequencing
of the TSPYL2 exons, and in silico splice site analysis of the identified sequence
variants.
In the behavioral test battery, our Tspyl2m mice were normal in social
ability, but showed enhanced hyperlocomotion after amphetamine injection, and
deficit in prepulse inhibition and cued fear conditioning. When expressed in
HEK293 cells, HA-TSPYL2 colocalized completely with endogenous CBP, but
not with p300 and pCREB. In mammalian two-hybrid assay,
pVP16(AD)-TSPYL2 interacted with GAL4(DBD)-CBP; however, HA-TSPYL2
did not immunoprecipitate with CBP. The luciferase assay data indicated that
TSPYL2 suppressed the transcription of CREB-target genes. Lastly, no
methylation was detected in the target sites in the TSPYL2 upstream sequence.
Seven TSPYL2 sequence variations being identified were not deleterious as
predicted by splice site analysis.
To sum up, our Tspyl2m mice were deficit in cued fear memory, a form of
associative memory. Moreover, they resembled the glutamatergic
antagonist-induced schizophrenic rodent models in having enhanced
hyperlocomotion after amphetamine injection, and deficit in prepulse inhibition.
TSPYL2 interacted with CBP and suppressed the CRE-luc activity. The
importance of TSPYL2 in XLMR has yet to be determined by larger studies. I
propose that TSPYL2 represses CREB-dependent gene expression via
sequestration of CBP as one of the possible mechanisms of how TSPYL2 causes
various behavioral phenotypes.published_or_final_version
Paediatrics and Adolescent Medicine
Master
Master of Philosophy
24
Deol, Jatinderpal. "Development of helper-dependent adenovirus for gene expression in muscle." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=33745.
Анотація:
Duchenne muscular dystrophy (DMD) is characterized by necrosis and progressive loss of muscle fibers. DMD patients have a mutation in the gene encoding dystrophin, a large membrane-associated cytoskeletal protein on the cytoplasmic side of the sarcolemma. Gene therapy using fully deleted adenoviral vectors shows great potential for the eventual treatment of DMD and other genetic diseases. These vectors are less immunogenic than their predecessors and have the capacity to carry large DNA inserts such as the full-length dystrophin (12 kb). However, the lack of viral genes results in a weakened and subsiding (short) transgene expression in muscle. Findings in the lung and liver have shown the adenoviral E4 region, in particular E4 open reading frame 3 (ORF3) to contribute to the maintenance of transgene expression. We constructed an adenovirus in which E4 ORF3 was reintroduced into a fully-deleted adenovirus along with full-length dystrophin (AdCBDysORF3). Dystrophin levels produced by AdCBDysORF3 were found to be not sustained in mdx mice, dropping significantly by day 90. However, expression levels did increase when AdCBDysORF3 was complemented with other viral proteins such as EIB. Likewise, increasing the expression of the primary adenovirus receptor (CAR) in muscle also resulted in a higher initial dystrophin expression in myofibers.
25
Purtill, Frances Siobhan. "Regulation of cell cycle-dependent gene expression in schizosaccharomyces pombe." Thesis, University of Newcastle Upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542210.
26
Hoo, Lai-chong Ruby, and 何麗莊. "Transcriptional regulation of the human glucose-dependent insulinotropic polypeptide gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31224428.
27
Brading, Penelope. "Functional analysis of Cf gene-dependent defence responses in tomato." Thesis, University of East Anglia, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389348.
28
Durrant, Wendy E. "Gene expression profiling of the Cf-9 dependent defence response." Thesis, University of East Anglia, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323392.
29
Hoo, Lai-chong Ruby. "Transcriptional regulation of the human glucose-dependent insulinotropic polypeptide gene." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22266665.
30
Bezerra, Milena Gurgel Teles. "Estudo do gene GPR54 nos distúrbios puberais centrais idiopáticos." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-24112008-113934/.
Анотація:
O complexo de sinalização kisspeptina-GPR54 é um regulador chave para ativação dos neurônios de GnRH e do eixo reprodutivo. Mutações inativadoras no GPR54 foram identificadas em pacientes com hipogonadismo hipogonadotrófico normósmico isolado (HHIn). A partir desse achado, hipotetizamos que mutações ativadoras no GPR54 resultariam na liberação prematura de GnRH e, conseqüentemente, no aparecimento de puberdade precoce, dependente de gonadotrofinas (PPDG). No presente estudo, investigamos a presença de mutações ativadoras e/ou polimorfismos em pacientes com PPDG, assim como a presença de mutações inativadoras e/ou polimorfismos em pacientes HHIn ou retardo constitucional do crescimento e desenvolvimento puberal (RCCP). Cento e catorze pacientes com distúrbios puberais centrais idiopáticos foram selecionados, sendo 53 com PPDG, 33 com HHIn e 28 com RCCP. Cento e cinqüenta controles brasileiros que relatavam desenvolvimento puberal normal foram estudados. A região codificadora do GPR54 de todos os pacientes foi amplificada utilizando-se oligonucleotídeos intrônicos específicos, seguida de purificação enzimática e seqüenciamento automático. No grupo de puberdade precoce, identificamos uma nova variante em heterozigose no exon 5 do GPR54, que se caracterizou pela troca do aminoácido arginina por prolina na posição 386 (R386P) do receptor. Esta substituição foi encontrada em uma menina adotada com PPDG e estava ausente nos controles normais. Estudos in vitro demonstraram que as quantidades de fosfatidil-inositol (IP) e o grau de fosforilação da quinase regulada por sinal extracelular (pERK) em condições basais não foram significativamente diferentes entre as células transfectadas com o receptor selvagem ou com o receptor contendo a mutação R386P, indicando que não havia ativação constitutiva do receptor. No entanto, estudos por tempos mais prolongados demonstraram que a quantidade de IP e o grau de pERK permaneceram significativamente mais altos nas células transfectadas com o receptor mutante quando comparadas ao selvagem, indicando ativação da sinalização intracelular, porém por um mecanismo não-constitutivo. No grupo de hipogonadismo, duas novas variantes foram identificadas em três pacientes. Uma mutação do tipo inserção/deleção (indel) em homozigoze no sítio aceptor de splicing no intron 2 (IVS2-4_-2delGCAinsACCGGCT) do GPR54 foi identificada em dois irmãos com HHIn. Uma troca em heterozigose, E252Q, foi identificada em um paciente com HHIn esporádico. As duas alterações estavam ausentes no grupo controle. Polimorfismos foram encontrados nos pacientes com RCCP. Em conclusão, descrevemos a primeira mutação ativadora do GPR54 associada ao fenótipo de PPDG. Descrevemos uma nova mutação inativadora em sítio de splicing em pacientes com HHIn, entretanto mutações inativadoras do GPR54 são uma causa rara de HHIn.The kisspeptin-GPR54 signaling complex is a gatekeeper of pubertal activation of GnRH neurons and of the reproductive axis. Inactivating mutations in the GPR54 receptor were identified in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH). Based on this observation, we hypothesized that gain-of-function mutations of the human GPR54 receptor might be associated with premature activation of GnRH release, leading to gonadotropin-dependent precocious puberty (GDPP). In the present study, we investigated the presence of GPR54 activating mutations or polymorphisms in patients with GDPP and inactivating mutations or polymorphisms in patients with nIHH or constitucional delay of puberty (CDP). A hundred fourteen patients were selected; 53 with GDPP, 33 with nIHH and 28 with CDP. A hundred and fifty Brazilian controls who reported normal pubertal development were also studied. The entire coding region of GPR54 of all patients was amplified using specific intronic oligonucleotides followed by enzymatic purification and automated sequencing. We have identified a novel variant in heterozygous state in exon 5 of GPR54, R386P, in an adopted girl with GDPP. This substitution was absent in all controls. Basal inositol phosphate (IP) and phosphorilated extracellular signalregulated kinase (pERK) levels in cells transfected with WT or R386P GPR54 were not significantly different indicating that there was not a constitutive activation of the receptor. However, studies performed in more prolonged times demonstrated that the IP and the pERK levels were significantly higher in cells transfected with the mutant receptor when compared to the wild type, indicating that the signaling pathway was still activated although by a non-constitutive mechanism. In the nIHH cohort, we have identified two novel variants in three patients. The first variant was an insertion/deletion (indel) in homozygous state within the constitutive acceptor splice site of intron 2 of GPR54 (IVS2-4_-2delGCAinsACCGGCT) identified in two male siblings with nIHH. The second variant was the change E252Q in heterozygous state in a patient with sporadic nIHH. Both alterations were absent in the control population. We have found only polymorphisms in patients with CDP. In conclusion, we have described the first activating mutation in GPR54 associated with the GDPP phenotype. We have also described a novel splice site inactivating mutation in patients with nIHH however, inactivating mutations of GPR54 represent a rare cause of nIHH.
31
唐思慧 and See-wai Cindy Tong. "Over-expression of the forkhead box transcription factor foxM1 activates expression of the cyclin-dependent kinase inhibitorp16INK4a." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970795.
32
林秀華 and Sau-wah Selma Lin. "Modulation of cyclin expression by over-expression of the forkhead boxtranscription factor FoxM1." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B31224817.
33
Tong, See-wai Cindy. "Over-expression of the forkhead box transcription factor foxM1 activates expression of the cyclin-dependent kinase inhibitor p16INK4a." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B2517647x.
34
Rudd, S. A. G. "Towards a functional analysis of the host-encoded RNA-dependent RNA polymerase." Thesis, University of East Anglia, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327521.
35
Bazov, Igor. "Epigenetic Dysregulations in the Brain of Human Alcoholics : Analysis of Opioid Genes." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-270321.
Анотація:
Neuropeptides are special in their expression profiles restricted to neuronal subpopulations and low tissue mRNA levels. Genetic, epigenetic and transcriptional mechanisms that define spatiotemporal expression of the neuropeptide genes have utmost importance for the formation and functions of neural circuits in normal and pathological human brain. This thesis focuses on regulation of transcription of the opioid/nociceptin genes, the largest neuropeptide family, and on identification of adaptive changes in these mechanisms associated with alcoholism as model human pathology. Two epigenetic mechanisms, the common for most cells in the dorsolateral prefrontal cortex (dlPFC) and the neuron-subpopulation specific that may orchestrate prodynorphin (PDYN) transcription in the human dlPFC have been uncovered. The first, repressive mechanism may operate through control of DNA methylation/demethylation in a short, nucleosome size promoter CpG island (CGI). The second mechanism may involve USF2, the sequence–specific methylation–sensitive transcription factor which interaction with its target element in the CpG island results in USF2 and PDYN co-expression in the same neurons. The short PDYN promoter CGI may function as a chromatin element that integrates cellular and environmental signals through changes in methylation and transcription factor binding. Alterations in USF2–dependent PDYN transcription are affected by the promoter SNP (rs1997794: T>C) under transition to pathological state, i.e. in the alcoholic brain. This and two other PDYN SNPs that are most significantly associated with alcoholism represent CpG-SNPs, which are differentially methylated in the human dlPFC. The T, low risk allele of the promoter SNP forms a noncanonical AP-1–binding element. JUND and FOSB proteins, which may form homo- or heterodimers have been identified as dominant constituents of AP-1 complex. The C, non-risk variant of the PDYN 3′ UTR SNP (rs2235749 SNP: C>T) demonstrated significantly higher methylation in alcoholics compared to controls. PDYN mRNA and dynorphin levels significantly and positively correlated with methylation of the PDYN 3′ UTR CpG-SNP suggesting its involvement in PDYN regulation. A DNA–binding factor with differential binding affinity for the T allele and methylated and unmethylated C alleles of the PDYN 3′ UTR SNP (the T allele specific binding factor, Ta-BF) has been discovered, which may function as a regulator of PDYN transcription. These findings emphasize the complexity of PDYN regulation that determines its expression in specific neuronal subpopulations and suggest previously unknown integration of epigenetic, transcriptional and genetic mechanisms that orchestrate alcohol–induced molecular adaptations in the human brain. Given the important role of PDYN in addictive behavior, the findings provide a new insight into fundamental molecular mechanisms of human brain disorder. In addition to PDYN in the dlPFC, the PNOC gene in the hippocampus and OPRL1 gene in central amygdala that were downregulated in alcoholics may contribute to impairment of cognitive control over alcohol seeking and taking behaviour.
36
Koterba, Kristen L. "Ligand- and phosphorylation-dependent modulation of estrogen receptor target gene expression." Connect to full-text via OhioLINK ETD Center, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=mco1139321651.
Анотація:
Thesis (M.S.)--Medical University of Ohio, 2005."In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Major advisor: Brian G. Rowan. Includes abstract. Document formatted into pages: iv, 57 p. Title from title page of PDF document. Bibliography: pages 49-56.
37
Szarzynska, Bogna, Lukasz Sobkowiak, Bikram Datt Pant, Salma Balazadeh, Wolf-Rüdiger Scheible, Bernd Müller-Röber, Artur Jarmolowski, and Zofia Szweykowska-Kulinska. "Gene structures and processing of Arabidopsis thaliana HYL1-dependent pri-miRNAs." Universität Potsdam, 2009. http://opus.kobv.de/ubp/volltexte/2010/4508/.
Анотація:
Arabidopsis thaliana HYL1 is a nuclear doublestranded RNA-binding protein involved in the maturation of pri-miRNAs. A quantitative real-time PCR platform for parallel quantification of 176 primiRNAs was used to reveal strong accumulation of 57 miRNA precursors in the hyl1 mutant that completely lacks HYL1 protein. This approach enabled us for the first time to pinpoint particular members of MIRNA family genes that require HYL1 activity for efficient maturation of their precursors. Moreover, the accumulation of miRNA precursors in the hyl1 mutant gave us the opportunity to carry out 3’ and 5’ RACE experiments which revealed that some of these precursors are of unexpected length. The alignment of HYL1- dependent miRNA precursors to A. thaliana genomic sequences indicated the presence of introns in 12 out of 20 genes studied. Some of the characterized intron-containing pri-miRNAs undergo alternative splicing such as exon skipping or usage of alternative 5’ splice sites suggesting that this process plays a role in the regulation of miRNA biogenesis. In the hyl1 mutant intron-containing pri-miRNAs accumulate alongside spliced primiRNAs suggesting the recruitment of HYL1 into the miRNA precursor maturation pathway before their splicing occurs.
38
Al-Ghazawi, Feras. "Roles of bromodomain in the regulation of p300-dependent gene expression." Thesis, University of Ottawa (Canada), 2009. http://hdl.handle.net/10393/28045.
Анотація:
The transcriptional coactivator p300 displays an intrinsic histone acetyltransferase activity. It contains an evolutionarily conserved bromodomain serving as a specific acelyl-lysine binding module for histones or transcription factors to facilitate chromatin remodeling and transcriptional activation. The function of p300 is required by a diverse set of promoters. However, roles of bromodomain in the function of p300 are yet to be fully determined. In this study, we utilize cell lines expressing either wild-type or bromodomain truncated p300 to examine the expression of several p300-dependent genes that are involved in cell cycle regulation. The effects of histone acetylation on the expression of these genes were also examined by utilizing histone deacetylase inhibitors. Our results suggest that p300 regulates genes through different mechanisms and that bromodomain has roles in the recruitment of p300 to target promoters, providing an indication that the role of bromodomain in p300-dependent transcription is determined by individual promoter context.
39
Kuschak, Theodore I. "c-Myc dependent genomic instability of the ribonucleotide reductase R2 gene." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0020/NQ53061.pdf.
40
Paul, Christine E. "Analysis of p75NTR-dependent apoptotic pathways and of p75NTR gene products." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=19468.
Анотація:
The p75 neurotrophin receptor (p75NTR) binds members of the neurotrophin family and plays important roles in the regulation of neuronal survival, apoptosis and growth during development and after nervous system injury. Many in vitro and in vivo studies have shown that p75NTR induces cell death, though the signaling events that link p75NTR activation to apoptosis are not thoroughly understood. p75NTR-dependent apoptosis is associated with an increase in Rac and Jun kinase (JNK) activity, and recent work from our laboratory has shown that the p75NTR interactor, NRAGE, activates a mitochondrial death pathway involving JNK-dependent cytochrome C release and activation of Caspase-9, Caspase-7 and Caspase-3. Despite this progress, several important details of p75NTR apoptotic signaling remain unknown. In particular, it is unclear what targets of p75NTR-dependent JNK activation result in mitochondrial cytochrome C release and caspase activation. BH3-domain-only proteins are members of the Bcl-2 family that induce the association of Bax and Bak which in turn facilitate release of mitochondrial proteins such as cytochrome C into the cytosol. Transcriptional activation of BH3-domain-only genes through c-Jun- or p53-dependent pathways is implicated in apoptosis in neuronal and non-neuronal systems. In the first part of this thesis, I examined whether p75NTR-induced apoptosis is correlated with accumulation of BH3-domain-only gene products. U373 human glioma cells and mouse cortical neurons were infected with adenovirus expressing p75NTR to constitutively activate p75NTR-dependent pathways, and alterations in mRNA levels of the BH3-domain-only family members Bim, Bmf, Hrk, Bik, Puma, and Noxa were determined by RT-PCR. The results from these experiments showed that p75NTRmediated cell death did not result in BH3-domain-only gene transcription. Subsequent studies in our laboratory established that the BH3-domain-only protein, Bad, is phosphorylated on Serine 128 in a JNK-dependent manner, and that this phosphorylation is a critical component of p75NTR-dependent apoptosis. The generation of animals that lack p75NTR expression has been a critical advance in understanding the in vivo role of this receptor. In the second part of this thesis, I analyzed the recently created p75NTRExonlv-/- mice, which were shown to produce a null mouse lacking all p75NTR gene products, in contrast to the previously constructed p75NTRExon1"-/- mouse, which maintains expression of an alternatively spliced form of p75NTR (s-p75NTR). Our studies revealed that 75NTRExonIV-/- mice continue to express a p75NTR gene product that encodes a truncated protein containing the p75NTR extracellular stalk region together with the entire transmembrane and intracellular domains. The gene product is initiated from a cryptic Kozak consensus/initiator ATG sequence within a region of Exon IV located 3' to the pGK-Neo insertion site, likely as a result of enhancer elements within pGK-Neo cassette. Characterization of this protein product indicated that it localized to the plasma membrane and overexpression of the p75NTRExonIV fragment in heterologous cells resulted in activation of JNK and cleavage of Procaspase 3, indicating that it can mediate pro-apoptotic effects in vivo. These results indicate that aspects of the p75NTRExonIV-/- phenotype may reflect a gain-of-function mutation rather than a loss of p75NTR function.
41
Giles, Tom. "Gene regulatory networks for wheat genotype-dependent effects of cold temperatures." Thesis, University of Nottingham, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576493.
Анотація:
Understanding and optimising the response of crops to climate change is of central importance in enhancing food security. A better understanding of how wheat genes influence traits is required to allow breeders to respond to socioeconomic issues. One aspect concerns adjusting flowering phenotypes to match predicted future climates. It is therefore crucial to understand this vernalisation process. The identification of the genes involved in the vernalisation response will be important for breeding crops able to cope with the effects of climate change. In this research project, bioinformatics methods were used to investigate the effects of decreasing temperatures and photoperiods on the transcriptomes of three different wheat varieties. The Affymetrix probe-sets associated with the known vernalisation genes and their expression profiles were characterised. Further analyses showed that gene expression varied significantly between wheat varieties. Genes involved in cold stress, cold acclimatisation, sugar / lipid metabolism and disease resistance have been identified. Probe-set Ta.17293.2.S1_at was a potential biomarker for vernalisation. In Arabidopsis, hundreds of vernalisation-related genes have been investigated. These were compaired to the probe-sets present on the Affymetrix wheat GeneChip® and a total of 184 putative wheat vernalisation-related genes were identified. As a step towards understanding the vernalisation process, a putative wheat network was constructed, of which several interactions were substantiated using co-expression correlation analysis. These results indicated that histone modification may be taking place, suggestive of an epigenetic switch. In addition, Artificial Neural Network inference was used to identify several novel candidate vernalisation genes. Of specific note was SPK1, a GTP binding protein. This was putatively associated with the expression of CDF2, a DOF-type transcription factor. In order to test the functions of CDF2 and SPK1, shRNAi constructs were developed to silence these genes in vivo. Transgenic wheat plants were analysed with T0 plants.
42
Worthington, Jenny. "Radiation-controlled gene expression : a novel approach to oxygenation-dependent radiotherapy." Thesis, University of Ulster, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342528.
43
Davies, Rhian Jane. "Analysis of the Schizosaccharomyces pombe DNA structure dependent checkpoint gene rad26." Thesis, University of Sussex, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297959.
44
Abraham, Richard. "Gene expression underlying experience dependent plasticity in the mouse barrel cortex." Thesis, Cardiff University, 2005. http://orca.cf.ac.uk/56023/.
Анотація:
Throughout the life of an organism the synaptic connections that link neurons are in a constant state of flux, being strengthened and weakened in response to external stimuli. This plasticity provides the central nervous system with a means of adaptability, allowing it to respond to changes in the external environment and is believed to underlie the processes of learning and memory (Lynch, 2004). Neuronal plasticity can be studied using the paradigm of vibrissal deprivation in rodents (Fox, 2002). The mystacial vibrissae are represented in layer IV of the somatosensory cortex by clusters of neurons, termed barrels, in which the majority of neurons are responsive to stimulation of only the corresponding vibrissae (Woolsey and Van der Loos, 1970). The deprivation of the vibrissae results in a shift in responsiveness of neurons in deprived barrels to stimulation of surrounding spared vibrissae, and potentiation of responses of neurons in spared barrels to stimulation of the corresponding (principal) vibrissae ie experience dependent plasticity (Fox, 1992, Simons and Land, 1987). It had previously been shown that, like other plasticity paradigms, gene transcription, mediated by the cyclic AMP Response Element Binding Protein (CREB), is associated with experience-dependent plasticity in the mouse barrel cortex (Barth et al., 2000). The finding that upregulation of a reporter gene, under the transcriptional control of CREB, following vibrissal deprivation conditions that induce plasticity, has been complementated with studies showing that deletion of CREB impairs plasticity in the barrel cortex (Glazewski et al., 1999). Using microarray technology, this study analysed the changes in expression of endogenous genes to vibrissal deprivation patterns that induce neuronal plasticity. It was found that significant upregulation of a sub-set of plasticity related genes (PRGs) occurs, as in CRE reporter gene studies, early in the time course of deprivation that leads to plasticity. Real-Time PCR has confirmed the upregulation of a number of these genes. Functional analysis has identified a significant over-representation of genes involved in protein synthesis from the group of PRGs. Further to this three of the PRGs have been identified as candidate plasticity genes in a number of paradigms. The products of these genes are key components of the extracellular matrix. This suggests that modifications to this fundamental part of the central nervous system may be the mechanism that results in experience dependent plasticity in the mouse barrel cortex.
45
Koterba, Kristen L. "Ligand- and Phosphorylation-dependent Modulation of Estrogen Reeptor Target Gene Expression." University of Toledo Health Science Campus / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=mco1139321651.
46
Williams, Kevin Jason. "NF- kB c-Rel dependent gene induction in the immune response." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1779835231&sid=6&Fmt=2&clientId=1564&RQT=309&VName=PQD.
47
Hertweck, Arnulf. "Dicer-dependent regulation of gene expression and development in T lymphocytes." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501208.
48
Jones, Richard Huw. "Developmental programming of type 2 diabetes associated genes." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608954.
49
Parry, David Alun. "Biochemical and functional analyses of p16INK4a, an inhibitor of cyclin D-dependent kinases." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243499.
50
Fahl, Willian de Oliveira. "Marcadores moleculares para a patogenia de vírus da raiva: relação entre períodos de incubação, carga viral e os genes codificadores das proteínas virais P e L." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/10/10134/tde-24072014-103209/.
Анотація:
A raiva é uma doença aguda, progressiva e infecciosa do sistema nervoso central de mamíferos, causada pelo vírus da raiva (RABV). Embora possa ser prevenida por vacina, continua sendo um grave problema de saúde pública, além de ser responsável pela morte de seres humanos e muitos outros animais, incluindo os de interesse econômico. Este estudo teve como objetivo avaliar a relação entre polimorfismos dos genes que codificam as proteínas P e L de amostras de RABV pertencentes a variantes antigênicas 2 e 3 e períodos de incubação e títulos em camundongos. Para isso, foram selecionadas amostras isoladas de diferentes reservatórios de raiva de mamíferos das Ordens Carnivora e Chiroptera e amostras de bovinos, de áreas endêmicas para o vírus da raiva. As sequências obtidas foram utilizadas para a construção de árvores filogenéticas para procurar os padrões de segregação de linhagens. Os resultados mostraram que não houve marcadores ou polimorfismos que explicam as variações nos períodos de incubação e de letalidade entre cepas pertencentes a variantes antigênicas 2 e 3. Esta informação pode ser usada para discussões sobre a importância de reservatórios de raiva, a dinâmica do vírus da manutenção e evolução das diferentes formas desta zoonose entre os animais infectados, contribuindo para um estudo mais aprofundado sobre a busca de marcadores moleculares para patogênese.Rabies is an acute, progressive and infectious disease of the central nervous system of mammals, caused by Rabies virus (RABV). Although preventable by vaccine, it remains a serious public health problem, and is responsible for the death of humans and many other animals, including those of economic interest. This study aimed to assess the relationship between polymorphisms in genes encoding the P and L proteins of RABV samples belonging to antigenic variants 2 and 3 and incubation periods and titers in mice. For this, samples isolated from different mammalian rabies reservoirs of the Orders Carnivora and Chiroptera and samples of cattle from endemic areas for rabies virus were selected. The sequences obtained were used to construct phylogenetic trees to search for the segregation patterns of strains. The results showed that there were no markers or polymorphisms that explain variations in incubation periods and lethality amongst strains belonging to antigenic variants 2 and 3. This information might be used for discussions about the importance of rabies reservoirs, the dynamics of the virus maintenance and evolution of the different forms of this zoonotic disease among infected animals, contributing to further study about the search for molecular markers for pathogenesis.